Preservation of an intact Atm-governed DDR determines treatment responses in vitro and in vivo. (A) 7-Amino-actinomycin D flow-based cytotoxicity analysis of the DDR⁺, DDR⁻, and NAC-protected control lymphomas as well as p53-null and Atm^−/− lymphomas measured at 19 hours of ADR exposure at the indicated concentrations in vitro (n = 3 individual samples per group). (B) Cellular and nuclear apoptotic morphology by hematoxylin and eosin staining (H.E., left) and visualization of apoptotic DNA strand breaks by the TUNEL reaction (right) in lymphoma sections of the indicated groups 4 hours after intraperitoneal administration of 300 mg/kg CTX. (C) Representative cytospin preparations of Bcl2-expressing DDR-competent versus Atm^−/− lymphoma cells exposed to ADR for 7 days or left untreated and stained for senescence-associated β-galactosidase activity. Original magnification × 200. (D) Time-to-relapse analysis of mice harboring lymphomas of the indicated groups after exposure to a single dose to a 4 Gy total body γ-irradiation (DDR-competent control lymphomas [ctrl^DDR+], n = 7; DDR-compromised control lymphomas [ctrl^DDR−], n = 6; Atm^−/− lymphomas, n = 11; NAC-protected control lymphomas [ctrl^NAC], n = 8). All quantitative data are mean ± SD; *P < .05.